Work

Editorial: Biofluid biomarkers for the diagnosis of neurodegenerative diseases: current status

Year: 2026

Type: editorial

Abstract: Disease is diagnosed only when a biomarker test reaches the pre-determined cut-off values. However, cut-offs may depend on demographics (e.g., sex, ancestry, ethnicity), medications used for the treatment of comorbidities [4], or the measurement platform used to carry out a given biomarker test [5]. These examples emphasize the need for conducting large scale studies across diverse populations that investigate several variables in parallel with sufficient statistical power for each variable.In addition to the parameters above, one must also consider biological and methodological criteria when developing or conducting biofluid marker measurements. First, there is the choice of matrix used, which include cerebrospinal fluid (CSF), blood, saliva (e.g., Gleerup [6]. The type of biomarker also determines the method used to conduct measurements. For example, DNA and RNA molecules are often measured via PCR methods, while native and modified proteins can be analyzed either by singleplex or multiplex ELISA methods, mass spectrometry, enzymatic activity assays, immunohistochemistry, immunocytochemistry, cell sorting, or oligomerization/seed amplification assays. Each method and measurement platform displays unique biophysical parameters making them more or less relevant to the measurement of a given biomarker: this includes lower and higher limits of detection, possible interferences due to matrix effects, binding affinity of proprietary antibodies, and pre-processing methods.In aggregate, lessons learned #1: multiple parameters need to be considered in the development and use of biomarkers for NDDs. In recent years, it has become increasingly apparent that panels of multimodal markers hold stronger potential than single markers in either context of use (e.g., Wang et al. (https://www.frontiersin.org/journals/agingneuroscience/articles/10.3389/fnagi.2026.1728675/full)), which has stimulated many business opportunities to identify highly pertinent biomarker panels for the improved diagnosis of NDDs. This is highlighted by the approval by the FDA in recent years of CSF-and blood-based biomarkers for the diagnosis of Alzheimer's disease. Consequently, more physicians request biofluid-based biomarkers for patients presenting with memory complaints and integrate the test results in their stepwise algorithms used to develop personalized treatment plans. For example, the two currently FDA-approved immunotherapies for the treatment of Alzheimer's require administration at early stage of the disease. Thus, physicians need to first diagnose patients with Alzheimer's disease, then ascertain whether the disease is early stage. In the future, physicians may need to consider treatment initiation for biomarker-positive asymptomatic patients. In such a case scenario, it will be important to determine whether a positive test result is both associated with neuropathology and prognostic of future conversion to symptoms.Lessons learned #2: this Research Topic of papers illustrate the current state of research on biofluid biomarkers for NDDs. While some biomarkers are now used in daily clinical practice for Alzheimer's management, there remain numerous areas of investigation to develop novel platforms and biomarkers to cover the full spectrum of NDDs and determine their context of use as well as their longitudinal trajectory both in disease and non-disease states. Since most NDDs have no cure at present, the most sought-after approach is the modification of lifestyles to either slow down or reverse early disease. Such paradigms may require the measurement of biomarkers among patients suffering NDDs, and also their family members who are often exposed to similar lifestyle and microenvironment (e.g., Chen et al. (https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2026.1763253/full)).Lessons learned #3: research on biofluid biomarkers for NDDs is still at its infancy and will require numerous additional, carefully designed studies to reach a stage of clinical development where multiple NDDs can be screened or diagnosed using multimodal panels of markers from a single biofluid collection. Furthermore, the development of biofluid biomarkers is an opportunity to identify cost-effective makers that can be used in patient stratification strategies and to assess treatment efficacy in clinical trials.

Source: Frontiers in Neuroscience

DOI: 10.3389/fnins.2026.1985558

Authors: Boris Decourt, Michelle M. Mielke, Paul Desmond Slowey, Marwan N. Sabbagh

Institutions: Texas Tech University Health Sciences Center, Wake Forest University Health Sciences, Wake Forest University, Oasis Diagnostics (United States), Barrow Neurological Institute

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801